The present invention relates to novel substituted quinolinecarboxylic acid derivatives having antibacterial activity.
Since the introduction of nalidixic acid in 1963, a considerable number of patents and scientific papers have been published on compounds having a 1-substituted-1,4 dihydro-4-oxopyridine-3-carboxylic moiety, collectively known as quinolone. Many of these compounds have been shown to have significant antibacterial activity. The structure-activity relationship of quinolone compounds has been reviewed by Schentag et al., Res. Clin. Forums, 7, (2), 9(1985).
At one time it was believed that substitution at the C-2 position of a substituted quinoline carboxylic acid led to inactive compounds, Metscher et al., J. Med. Chem. 21, 485(1978). However, U.S. Pat. No. 4,426,381 to Matsumura et al., discloses a compound having a thiazoline moiety connecting the C-2 substituent to the N-1 position. This compound was shown to have good antibacterial activity. Additionally, Chu et al., J. Heterocyclic Chem., 24, 1537(1987) discloses compounds where the C-2 and N-1 positions are bridged by an alkylene chain. The compounds of the present invention comprise novel improvements in which the C-2 and N-1 positions are bridged by an aromatic substituent.